Localization and characterization of neuropeptide Y/peptide YY receptors in the brain of the smooth dogfish ( Mustelis canis)

Multiple receptor subtypes specific for the neuropeptide Y (NPY)/peptide Y (PYY) family of peptides exist in mammals, but little is known about the distribution of this receptor family in other vertebrates. Saturable binding sites for 125I-labeled porcine PYY were localized in frozen sections of the brain of the smooth dogfish ( Mustelis canis) by radioligand binding and autoradiography. Saturable 125I-porcine PYY binding sites were distributed widely in the cerebral hemispheres, optic lobes, hypothalamus, cerebellum and hindbrain. Binding was saturable, specific for PYY and related peptides, and of high affinity ( K d = 2.53 nM). The specificity of the binding site was analyzed by performing competitive inhibition experiments with nonradioactive PYY, NPY, and [Leu 31, Pro 34]-NPY and NPY 13–36, synthetic peptide analogs specific for the mammalian Y1 and Y2 receptor subtypes, respectively. Saturable 125I-porcine PYY binding sites in all regions of the dogfish brain closely resembled the mammalian Y1 NPY receptor subtype in specificity for these substances. There was no evidence for expression of multiple receptor subtypes. We conclude that a single receptor specific for the NPY PYY family of peptides is widely expressed in the smooth dogfish brain and that this receptor closely resembles the mammalian Y1 receptor subtype, suggesting that the Y1 receptor is the ancestral receptor in this family.